An injectable: In situ lipid phase transition system for sustained delivery of dabigatran etexilate with low burst release

Abstract

Controlling initial burst release remains one of the greatest challenges in developing in situ-forming parenteral depot formulations. Here an injectable lipid phase transition system (LPTS) was fabricated to provide sustained release of dabigatran exilate (DABE) with low burst release. LPTS was prepared in a low-viscosity injectable state by simple mixing of sorbitan monooleate and phospholipids with ethanol. After subcutaneous injection, the liquid LPTS underwent a phase transition in situ and formed a semi-solid mesophase, creating a drug-release depot. The physicochemical properties of DABE-LPTS were investigated using rheological techniques. Release profiles in vitro indicated that DABE-LPTS has suitable controlled release properties. Pharmacokinetic studies showed that DABE-LPTS significantly reduced the initial burst release after subcutaneous injection in rats. Pharmacodynamic studies showed that single administration of DABE-LPTS exerted anticoagulant effects in rats lasting 1 week. DABE-LPTS showed good biocompatibility in vitro and in vivo. Thus, the LPTS-based depot system shows promise for sustained DABE delivery with low burst release.